Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, life-threatening disorder caused by drugs. In the present study, we tried to explore the types of DRESS-inducing drugs, incubation period, features of skin rashes, accompanying visceral damage, and effectiveness of glucocorticoid therapy so as to inform clinical practice.
Methods: Patients diagnosed with a drug-induced rash, dermatitis, and DRESS admitted to our hospital from January 2006 to December 2015 were included in the study. The diagnosis followed the criteria and scoring system set by the European Registry of Severe Cutaneous Adverse Reactions. Statistical analyses were carried out using SPSS version 17.0 (IBM, Armonk, NY, USA), and a value of P < 0.05 was considered statistically significant.
Results: Among 104 patients, 38 were male and 66 female (aged 18–83 years). The latent period was 13 (interquartile range [IQR]: 10–17) days. The most common allergy-inducing drugs were antibiotics (n = 37, 35.6%), followed by antiepileptic drugs and traditional Chinese medicines (TCMs). Eighty-two cases (78.8%) had rash with area >50% body surface area (BSA). Liver damage occurred in 90% of cases. Patients were divided into oral antihistamine group and glucocorticoid/immunosuppressive agent/intravenous immunoglobulin (IVIG) group. Sex, age, incubation period, duration of hospital stay, and the number of patients with body temperature ≥38.5°C were not significantly different between the two groups. However, the number of patients meeting the criteria of “definite” and “probable” (χ2 = 5.852, P = 0.016), with an eosinophilic granulocyte count of ≥1.5 × 109/L (χ2 = 7.129, P = 0.008), and with rash area of >50% BSA (χ2 = 4.750, P = 0.029), was significantly different.
Conclusions: Antibiotics were associated with allergic reactions, but TCMs also had an important role. Allergy resulting from repeat use of the same drug was more severe with a shorter incubation period. The most typical rash was widespread erythematous papules. Liver damage accounted for >90% of cases.

Background: Fetal brain development is a complicated process that continues throughout pregnancy. Fetal sulcus development has typical morphological features. Assessment of fetal sulcus development to understand the cortical maturation and development by prenatal ultrasound has become widespread. This study aimed to explore a reliable method to assess cortical sulcus and to describe the normal sonographic features of cortical sulcus development in the human fetus between 18 and 41 weeks of gestation.
Methods: A cross-sectional study was designed to examine the fetal cortical sulcus development at 18–41 weeks of gestation. Ultrasound was used to examine the insula, sylvian fissure (SF), parieto-occipital fissure (POF), and calcarine fissure (CF). Bland-Altman plots were used for assessing the concordance, and the intraclass correlation coefficient was used for assessing the reliability.
Results: SF images were successfully obtained in 100% of participants at 22 weeks of gestation, while the POF images and CF images could be obtained in 100% at 23 weeks of gestation and 24 weeks of gestation, respectively. The SF width, temporal lobe depth, POF depth, and the CF depth increased with the developed gestation. The width of uncovered insula and the POF angle decreased with the developed gestation. By 23 weeks of gestation, the insula was beginning to be covered. Moreover, it completed at 35 weeks of gestation. The intra- and inter-observer agreements showed consistent reproducibility.
Conclusions: This study defined standard views of the fetal sulcus as well as the normal reference ranges of these sulcus measurements between 18 and 41 weeks of gestation. Such ultrasonographic measurements could be used to identify fetuses at risk of fetal neurological structural disorders.

Background: According to the renal phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (iMN) could be categorized into PLA2R-associated and non-PLA2R-associated iMN. This study aimed to examine whether the non-PLA2R-associated iMN had any difference in clinical features compared with PLA2R-associated iMN.
Methods: A total of 231 adult patients diagnosed as iMN were recruited to this retrospective study. Renal PLA2R expression was examined by immunofluorescence. Among these patients, 186 (80.5%) with complete baseline clinical data were used for further study. Urinary protein excretion, serum albumin, and creatinine were analyzed. For those patients with follow-up longer than 1 year, the relationship between PLA2R and response to immunosuppressants were analyzed. The t-test was used for parametric analysis and the Mann-Whitney U-test was used for nonparametric analysis. Categorical variables were described as frequencies or percentages, and the data were analyzed with Pearson's Chi-square test or Fisher's exact test.
Results: Of the 231 iMN patients, 189 showed renal detectable PLA2R expression (81.8%). The baseline serum creatinine, serum albumin, and urine protein excretion were not significantly different between PLA2R-associated (n = 145) and non-PLA2R-associated iMN patients (n = 41). However, about 1/3 of the non-PLA2R-associated iMN had abnormal serological tests, significantly more common than PLA2R-associated iMN (31.7% vs. 8.3%, P = 0.000). The non-PLA2R-associated iMN had lower C4 levels compared with PLA2R-associated iMN (P = 0.004). The non-PLA2R-associated iMN patients also showed a better response to immunosuppressants (complete remission [CR] 42.9%; partial remission [PR] 14.3%) compared with PLA2R-associated iMN (CR 3.2%; PR 48.4%, P = 0.004) at the 3rd month.
Conclusions: There were no significant differences in serum creatinine, albumin, and urine protein excretion between PLA2R-associated and non-PLA2R-associated iMN, while the non-PLA2R-associated iMN patients showed more abnormal serological tests. The non-PLA2R-associated iMN seemed to respond more quickly to the immunosuppressive therapy compared with PLA2R-associated iMN.

Objective: Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment.
Data Sources: Studies of the association between PD-1/PD-L1 and sepsis published up to January 31, 2017, were obtained by searching the PubMed database.
Study Selection: English language studies, including those based on animal models, clinical research, and reviews, with data related to PD-1/PD-L1 and sepsis, were evaluated.
Results: Immunomodulatory therapeutics could reverse the deactivation of immune cells caused by sepsis and restore immune cell activation and function. Blockade of the PD-1/PD-L1 pathway could reduce the exhaustion of T-cells and enhance the proliferation and activation of T-cells.
Conclusions: The anti-PD-1/PD-L1 pathway shows promise as a new target for sepsis treatment. This review provides a basis for clinical trials and future studies aimed at revaluating the efficacy and safety of this targeted approach.

Background: Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.
Methods: Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality.
Results: In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094–1.886), age (OR: 1.046, 95% CI: 1.036–1.057), and presence of DN (OR: 1.837, 95% CI: 1.322–2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346–0.989), hemoglobin (OR: 0.974, 95% CI: 0.967–0.981), albumin (OR: 0.939, 95% CI: 0.915–0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070–0.386) were protective factors based on a multivariate analysis.
Conclusions: Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Background: Endometriosis (EMs) is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance of ectopic endometriotic lesions. Transforming growth factor-beta 1 (TGF-β1) plays a major role in the etiology of EMs. We aimed to determine whether TGF-β1 affects EMs development and progression and its related mechanisms in hypoxic conditions.
Methods: Endometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-β1 or TGF-β1 inhibitors. The messenger RNA (mRNA) and protein expression levels of TGF-β1, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) were measured. A Dual-Luciferase Reporter Assay was used to examine the effect of TGF-β1 and hypoxia on a VEGF promoter construct. Student's t-test was performed for comparison among groups (one-sided or two-sided) and a value of P < 0.05 was considered statistically significant.
Results: TGF-β1, VEGF, HIF-1α mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue (t = 2.16, P = 0.042). EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein (t = 6.84, P = 0.023). VEGF mRNA levels increased 12.5% in response to TGF-β, whereas the combined treatment of hypoxia/TGF-β1 resulted in a much higher production (87.5% increases) of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-β1 (2.6-fold, t = 6.08, P = 0.032) or hypoxia (11.2-fold, t = 32.70, P < 0.001), whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect (18.5-fold, t = 33.50, P < 0.001).
Conclusions: The data support the hypothesis that TGF-β1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-β1 and hypoxia is taking place at the transcriptional level.

Background: Primary anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a chronic autoimmune disease associated with multisystem dysfunction. Renal involvement is common and closely associated with outcome. The purpose of this study was to investigate the clinical determinants of mortality of patients with AAV-related renal injury in the first 2 years after diagnosis in a single West Chinese center.
Methods: Demographic and laboratory parameters of 123 consecutive patients with AAV-related renal injury diagnosed in Renal Division and Institute of Nephrology, Sichuan Provincial People's Hospital between 2004 and 2012 were collected retrospectively. All patients were followed up for 2 years after diagnosis. Survivors were compared with nonsurvivors to identify the clinical baseline variables associated with mortality. Multivariate Cox regression model was used to determine the independent predictors of mortality.
Results: Of the 123 patients, 46 (37.4%) died by the end of 2 years after diagnosis, with 41 (33.3%) patients dying within the first 12 months. In comparison with the survivors, Birmingham Vasculitis Activity Score (BVAS), the incidence of pulmonary hemorrhage and digestive system (DS) involvement, serum creatinine, and erythrocyte sedimentation rate were significantly higher in nonsurvivors, whereas lymphocyte counts, hemoglobin, and complement 3 (C3) were significantly lower. Renal replacement therapy was more common in nonsurvivors. High BVAS (hazard ratio [HR] = 1.058, 95% confidence interval [CI]: 1.002–1.117; P = 0.042), pulmonary hemorrhage (HR = 1.970, 95% CI: 1.033–3.757; P = 0.04), DS involvement (HR = 2.911, 95% CI: 1.212–6.911; P = 0.017), and serum creatinine >400 μmol/L (HR = 2.910, 95% CI: 1.271–6.664; P = 0.012) were independent predictors of death in patients with AAV-related renal injury.
Conclusions: Patients with AAV-related renal injury have high early mortality. Those with high BVAS (particularly with pulmonary or DS involvement) and serious renal dysfunction should receive aggressive therapy and careful monitoring to reduce the occurrence of adverse events and improve prognosis.

Background: The ST-segment elevation myocardial infarction (STEMI) patients due to stent thrombosis (ST) remain a therapeutic challenge for a clinician. Till date, very few researches have been conducted regarding the safety and effectiveness of primary percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES) for STEMI caused by very late ST (VLST). This retrospective study evaluated the safety, efficacy, and outcomes of primary PCI with second-generation DES for STEMI due to VLST compared with primary PCI for STEMI due to de novo lesion.
Methods: Between January 2007 and December 2013, STEMI patients with primary PCI in Fuwai Hospital had only second-generation DES implanted for de novo lesion (558 patients) and VLST (50 patients) were included in this retrospective study. The primary end points included cardiac death and reinfarction. The secondary end points included cardiac death, reinfarction, and target lesion revascularization. Continuous variables were expressed as mean (standard deviation) or median (interquartile range) and compared by Student's t- test or Mann-Whitney U-test as appropriate. Categorical variables were expressed as counts and percentages, and comparison of these variables was performed with Chi-square or Fisher's exact test. A two-tailed value of P < 0.05 was considered statistically significant for all comparisons. Statistical analyses were performed by SAS software (version 9.4, SAS Institute Inc., Cary, USA) for Windows.
Results: In-hospital primary end point and the secondary end point were no significant differences between two groups (P = 1.000 and P = 1.000, respectively). No significant differences between two groups were observed according to the long-term primary end point and the secondary end point. Kaplan-Meier survival curves showed no significant difference between the two groups in the primary end point and the secondary end point at 2 years (P = 0.340 and P = 0.243, respectively). According to Cox analysis, female, intra-aortic balloon pump support, and postprocedural thrombolysis in myocardial infarction flow 3 were found to be independent predictors for long-term follow-up.
Conclusion: Primary PCI with second-generation DES is a reasonable choice for STEMI patients caused by VLST.

Recommendations on the Clinical Use of Compound Danshen Dripping PillsWriting Group of Recommendations of Expert Panel from Chinese Geriatrics Society on the Clinical Use of Compound Danshen Dripping Pills 20th April 2017, 130(8):972-978DOI:10.4103/0366-6999.204106 PMID:28397728

Background: Several studies concerning the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and male infertility risk have reported controversial findings. The present study was aimed to explore this association using a meta-analysis.
Methods: The PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched. Odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the strength of the association.
Results: A total of 3282 cases and 3268 controls in nine case-control studies were included. There was no significant association between GSTP1 Ile105Val polymorphism and male infertility in the overall population, but significant associations were found under the dominant (OR = 1.23, 95% CI = 1.04–1.46, I2 = 32.2%) and heterozygote (OR = 1.29, 95% CI = 1.08–1.53, I2 = 26.8%) models after excluding studies for which the data did not satisfy Hardy-Weinberg equilibrium (HWE). Similarly, subgroup analyses revealed no significant association in Asians or Chinese population although a significant association was apparent among Chinese population in studies with HWE under the heterozygote model (OR = 1.25, 95% CI = 1.03–1.52, I2 = 44.1%). Significant heterogeneity could be observed in some genetic models, but this heterogeneity was not significant when stratified by HWE. No evidence for publication bias was found.
Conclusions: The GSTP1 Ile105Val polymorphism might not be associated with male infertility risk, and thus additional well-designed studies with larger sample size are warranted.

Background: In head and neck neoplasm survivors treated with brain irradiation, metabolic alterations would occur in the radiation-induced injury area. The mechanism of these metabolic alterations has not been fully understood, while the alternations could be sensitively detected by proton (1H) nuclear magnetic resonance spectroscopy (MRS). In this study, we investigated the metabolic characteristics of radiation-induced brain injury through a long-term follow-up after radiation treatment using MRS in vivo.
Methods: A total of 12 adult Sprague-Dawley rats received a single dose of 30 Gy radiation treatment to semi-brain (field size: 1.0 cm × 2.0 cm; anterior limit: binocular posterior inner canthus connection; posterior limit: external acoustic meatus connection; internal limit: sagittal suture). Conventional magnetic resonance imaging and single-voxel 1H-MRS were performed at different time points (in month 0 before irradiation as well as in the 1st, 3rd, 5th, 7th, and 9th months after irradiation) to investigate the alternations in irradiation field. N-acetylaspartate/choline (NAA/Cho), NAA/creatinine (Cr), and Cho/Cr ratios were measured in the bilateral hippocampus and quantitatively analyzed with a repeated-measures mixed-effects model and multiple comparison test.
Results: Significant changes in the ratios of NAA/Cho (F = 57.37, P<sub>g < 0.001), NAA/Cr (F = 54.49, P<sub>g < 0.001), and Cho/Cr (F = 9.78, P<sub>g = 0.005) between the hippocampus region of the irradiated semi-brain and the contralateral semi-brain were observed. There were significant differences in NAA/Cho (F = 9.17, P<sub>t < 0.001) and NAA/Cr (F = 13.04, P<sub>t < 0.001) ratios over time. The tendency of NAA/Cr to change with time showed no significant difference between the irradiated and contralateral sides. Nevertheless, there were significant differences in the Cho/Cr ratio between these two sides.
Conclusions: MRS can sensitively detect metabolic alternations. Significant changes of metabolites ratio in the first few months after radiation treatment reflect the metabolic disturbance in the acute and early-delayed stages of radiation-induced brain injuries.

What Has Shaken the Determination of Medical Students to Become a Doctor?Xin-Ye Xu, Wei Gao, Ai-Jing Zhang, Jing Huang, Ming Cui, Wei Zhao20th April 2017, 130(8):1001-1002DOI:10.4103/0366-6999.204109 PMID:28397733